www cymru gov uk NISCHR Academic Health Science

www. cymru. gov. uk NISCHR Academic Health Science Collaboration Launch Millennium Stadium Cardiff 3 March 2011

www. cymru. gov. uk Severnside Alliance for Translational Research (SARTRE) – A cooperative approach to working across institutions Professor Lars Sundstrom, Director of SARTRE

ØContext ØThe new landscape for therapeutics ØPartnerships and alliances ØContext for NISCHR-AHSC Prof. Lars Sundstrom ØSARTRE ØBackground ØWhat we are doing ØA few case studies Severnside Alliance for Translational Research www. Sartre. ac. uk

Context The View from academ Ø Research councils/NHS are focusing more on societal impact and translational funding Ø NISCHR/NIHR, WT, MRC-DPFS, NIH, IMI Ø Pharma’s productivity is not as expected Ø Early stage Biotech is facing problems Ø More willing to outsource pre clinical research and collaborate in R&D, Looking for options to engage with projects early. Ø Personalised medicine, diagnostic and pharmacodynamic markers have become critical. Ø Capital markets are very frosty, challenging biotechs as a vehicle for therapeutics development. Creates new opportunities for the public sector.

Academic institutions are not companies! Lab science (Bench) Research Ø Reverse Patients (Bedside) Products Mission - To pursue and share knowledge and understanding, both for their own sake and to help individuals and society fulfil their potential. Ø Ø Ø Forward Translational research -The acceleration of advances in (medical) research towards societal benefit. In order to perform basic research we need to demonstrate effective translation. Thus translation is an integral part of our mission.

Translational disconnec Ø Discovery is done in cell free systems Ø Then tested in simple unicellular systems Ø Results are confirmed in animal models Ø Then tested in a few humans Ø Then given to lots of different humans This is not leading to new treatments

Ø Challenges in translation to hu Not everyone responds the same way to drugs Ø Beneficial Ø Adverse Ø Non–responders Ø Treatment response markers Ø Predicting response from model systems Ø Better test systems Ø Better understanding of how to use them Ø Validation with clinical end points Ø Better understanding of disease biology Ø Linking Clinical and laboratory sciences Ø Ø Forward translation Back translation Surrogate end points Pharmacodynamic markers Ø Applying knowledge from genomics Translational science is addressing these gaps Ø Systems biology

Academia is uniquely placed to drive tran science innovation Source of BUT ◦ ◦ Disease mechanisms New targets New biomarkers New technologies Clinical expertise ◦ We need to develop a new culture ◦ And new ways of working ◦ Patient stratification ◦ Experimental medicine ◦ Clinical research Training ◦ New translational scientists In academia and industry NISCHR/AHSC

Increasing R&D costs is leading to mor collaborative models with industry. Cooperative models Open innovation models Melese et al. Nature medicine 2009 15; 5 502 -507 Munos et al. Nature Reviews Drug Discovery 2010 9; 203 -214

In-house Vs Collaborative model Interactions are implicit Traditional in-house model University Patho physiology Target Academic Expertise In vivo model Assay Screen SME/Pharma Hit NHS Proof of concept in human Lead Candidate Development & Tox Company Expertise NISCHR/AHSC Post Market Drug Benefit Phase III CRO-Pharma

Major problem- Developmen actually increasing We are all looking for a new model Certainly public private partnerships Basic Research Discovery Research Shift of Pharma Needs Commercial Development Shift of Pharma Resources “Valley of Death” -Development Gap ©Obama Administration ‘How will this be funded? ’

Portfoilo approaches to Joint value creation Public sector Partners: Universities NHS R&D Partners NISCHR/Charities RCs MRC/BBSRC/EPSRC/TSB EU Value Creation License Product New Co Partnership Private sector partners: Local(SMEs)/TSB/KTP International (Pharma/Biotech/Medtech) ØSynergy, Critical mass, Scale and Collaboration are byproducts ØActive project management is essential with multiple actors ØFlexible funding mechanisms are essential to catalyse collaborations

SARTRE An example of effective inter-university cooperation between Bristol and Cardiff Universities to advance translational research together. Funding from WAG and MRC devoloved DPFS funding. Creation of a unique competence network. Leveraging shared resources for maximum. mutual benefit. Critical mass for attracting new govt. funding. Portal for realizing opportunities with industry. Together we are stronger

SARTRE is about building a Industry Bristol Basic SARTRE Clinica ‘The start of a federated approach’

How we strengthen the links Mapping Scouts Web based Networking Partnering Finding Partners Alliance management Demonstration Select Pilot Projects Funding Project management Follow on strategies Linking Focus groups Networking meetings Teaching Training Seminars Enterprise and Innovation

How we strengthen the links Mapping Scouts Web based Networking Partnering Finding Partners Alliance management Demonstration Select Pilot Projects Funding Project management Follow on strategies Linking Focus groups Networking meetings Teaching Training Seminars Enterprise and Innovation

Networking meetings to explore Larger scale networking areas of synergy (Clinical>>Basic>>Regional) ◦ Dec 2010 (Translational technology platforms) with Mediwales and Cardiff University SOM I&E. ◦ Cancer research (4) - (Medicinal chemistry) 14 th May @Bath ◦ DPFS- (Showcase) Newport May 22 nd ◦ I 4 (3) - (Diabetes and Cardiovascular) Cardiff June 24 th Focus groups ◦ Feb 2011 Kick of meeting SW Critical care alliance (Bristol/Bath/Cardiff/Brimingham) Sepsis sample bio-repository

How we strengthen the links Mapping Scouts Web based Networking Partnering Finding Partners Alliance management Demonstration Select Pilot Projects Funding Project management Follow on strategies Linking Focus groups Networking meetings Teaching Training Seminars Enterprise and Innovation

Project funding Strategic Projects ◦ Funding for a PET specialist (PETIC-Cardiff) WAG funding for Patricia Sancjez-Roa (Madrid) Funding for a demonstration project from Bristol. ◦ Protein production unit (CBS-Cardiff) Funding for demonstration projects from Bristol. MRC DPFS – Devolved portfolio ◦ Proof of concept studies (£<30 K) ◦ Larger projects (£<500 K)

MRC Translational Fund Devolved Portfolio £ 2 M 2009/10 -2012

Building an early stage portfolio Increased likelihood of further funding and partnering Later stage Explotation Phase Up to £ 3 M Later stage Mid stage Partnerships Proof of concept £ 150 -£ 500 K ~1 -2 3 V. Early stage Full projects Speculative Up to £ 30 K Years Several Miles 5 Works under a framework agreement for IP Personnel etc… Between Bristol and Cardiff Universities Seed corn Projects, 1 year 1 mile 15

Therapeutics Projects – (D Loc Lead Project Durat ion Objective Translation (traction so far) Mc. Guiga n Novel Protides for Colorectal Cancer 24 M New lead series (IP on compounds) Ongoing Allen Trk. A antagonists for arthritic pain 22 M New lead series (IP on compounds) Hallet Calpain-1 antagonists in inflammation in arthritis 12 M New indication for existing compounds Under discussion Mc. Guiga n Novel antivirals CMV and VZV 30 M New indication for existing compounds Further funding Blain B. Frereana Natural product antiinflammatory in arthritis 9 M Build data package for licensing Co-funded by a company from outset. Fergusson Polymer peptides as antibacterial agents 12 M Novel drug delivery system (IP on novel Further funding Under discussion

Tools and Pre-Clinical Projec Loc Lead Project Duration Objective Translation Robinson Back-translation of a human anxiety model to an animal model 18 M A new translational animal model of anxiety Ongoing Whone Measuring impulsivity in humans with Parkinsons. 12 M A new diagnostic software tool Paton Cerebral artery stenosis and hypertensioni in man 12 M Demonstrate a link in hypertensive patients in a small clinical study Ongoing A method for modifying protein therapeutics 12 M Exemplify Trine. X method with a therapeutic protein Ongoing M. Jones Correlation SSRT in animals with human EEGs. 12 M A common translational end point for cortical dysfunction Tavare EGF signalling in breast cancer as a response indicator 36 M A patient stratification tool D. Jones Ongoing Partnered with Pharma Under discussion

How we strengthen the links Mapping Scouts Web based Networking Partnering Finding Partners Alliance management Demonstration Select Pilot Projects Funding Project management Follow on strategies Linking Focus groups Networking meetings Teaching Training Seminars Enterprise and Innovation

An corn project example Seed ◦ Matt Jones, Lynsey Forsyth (Bristol University), Lawrence Wilkinson, Trevor Humby (Cardiff University), Liz Couthard (NBHT). ◦ Development of a common translational end point between animal models and humans for EEG evaluation of antipsychotics. Now being co-developed with Janssen (Belgium) ◦ Dr. Trevor Howe seconded to build a partnership with SARTRE ◦ Janssen/SARTRE supplying direct funding, tool compounds and input in kind to the project ◦ Will result in validation of the models being developed.

Industry Partner Company champion Translator University 1 Tech Transfer Translator Tech Transfer Translational research Hub R&D Mangers University 2

All stakeholders will need to work t the search for new treatments Academia Patients New Ideas New Targets Need for new medicines Stakeholder organizations Clinical resources Govt/Markets A new co-operative model is evolving Pharma Cost pressures Partnerships are the key to success Drug Discovery AHSC SARTRE are examples Generics Development Resources Personalised

Thank You L. Sundstrom@Bristol. ac. uk +44 (0)7595 245263 www. sartre. ac. uk